As is known, all of the antiphlogistic agents hitherto used have the common disadvantage of causing gastrointestinal haemorrhages or ulcers. The ulcerogenic side-effects of 1-(chlorobenzoyl)5-methoxy-2-methyl-indole-3-yl-acetic acid (indomethacin), 4-butyl-1,2-diphenyl-pyrazolidine-3,5-dione (phenylbutazone) and acetylsalicylic acid have been reported in numerous publications (Bonfils et al: Bull. Mem. Soc. Med. Hosp. Paris, 5, 114 (1955); Somogyi et al: J. Pharm. Pharmacol. 21, 122 (1969); R. Nath: Studies on the Pharmacology of Inflammation, M.D. Thesie Lucknow University, Lucknow, India (1970)' Lee et al.: Arch. Int. Pharmacodyn. 19, 370 (1971); Bhargava et al.: European J. of Pharmacol. 22, 191 (1973); Katz et al.: Clin. Pharm. Ther. 6, 25 (1965); Leonard et al.: Clin. Pharmocol. Ther, 14, No. 1, 62 (1973).
Indomethacin is the most potent ulcerating compound among approved non-steroidal antiinflammatory agents. Its toxicity is directly related to its ulceration proclivities.
In prolonged treatments of various arthritic conditions two or more difficult antiphlogistic agents can sometimes be admininstered simultaneously to the patients. The antiphlogistic effects arising upon the simultaneous administration of indomethacin and acetylsalicyclic acid were investigated first in animal tests (Mielons et al.: J. Pharm. Pharmac. 20, 567 (1968); Swingle et al.: J. Pharmacol. Exp. Ther. 172, 423 (1970); Yesair et al.: Biochem. Pharm. 19, 1591 (1970). Since the oedema tests had not indicated the additivity of antiphlogistic effects, clinical tests were performed in order to elucidate this question (Champion et al.: Clin. Pharm. and Ther. 13, 239 (1972); Lindquist et al.: Clin. Pharm. and Ther. 15, 247 (1974). These clinical tests have shown that the blood indomethacin level is not affected by the simultaneous administration of acetylsalicylic acid, that is, these two types of antiphlogistic agents do not worsen the effects of one or the other.